The invention relates to methods and compositions useful for treating type 2 diabetes, obesity, and metabolic syndrome.
Daily consumption of fresh fruits, vegetables, seeds and other plant-derived ingredients of salads and juices is recognized as part of a healthy diet and associated with weight loss, weight management and overall healthy life styles. This is demonstrated clinically and epidemiologically in the “China Study” (Campbell, T. C. and Campbell T. M. 2006. The China Study: startling implications for diet, weight loss and long-term health. Benbella books. pp 419) where a lower incidence of cardiovascular diseases, cancer and other inflammatory-related indications were observed in rural areas where diets are whole food plant-based. The benefit from these is thought to be derived from the vitamins, fiber, antioxidants and other molecules that are thought to benefit the microbial flora through the production of prebiotics. These can be in the form of fermentation products from the breakdown of complex carbohydrates and other plant-based polymers. There has been no clear mechanistic association between microbes in whole food plant-based diets and the benefits conferred by such a diet. The role of these microbes as probiotics, capable of contributing to gut colonization and thereby influencing a subject's microbiota composition in response to a plant-based diet, has been underappreciated. In contrast to a plant-based diet, diets deficient in microbes such as the Western diet are associated with chronic inflammation, obesity, metabolic syndrome, type 2 diabetes (T2D) and sequelae.
Type 2 diabetes (T2D) is a systemic inflammatory condition where loss of insulin sensitivity leads to hyperglycemia and dyslipidemia, culminating in cell and tissue damage. Numerous studies have identified dysbiosis of the gut microbiome as a primary factor in the development of obesity and T2D, leading to a robust effort to develop microbiome-based therapeutic candidates for these conditions. In obesity and T2D, the gut microbiome is characterized by reduced microbial diversity and a shift in the equilibrium of Firmicutes and Bacteroidetes, the two most prevalent bacterial phyla residing in the colon. This altered microbial environment can result in increased energy harvest and intestinal permeability, as well as reduced production of enteroendocrine peptides and short chain fatty acids (SCFA), all of which can promote the inflammation and insulin resistance associated with obesity and T2D. Recent evidence indicates oral anti-diabetic drugs such as metformin may in part exert their effects through modulation of the gut microbiome.
What is needed are compositions and methods that treat T2D, obesity and metabolic syndrome by modulating a subject's microbiota composition away from that associated with a Western diet and toward one conferring the benefits of a plant-based diet.